Quite frequently, patients have to be treated regarding to their fluid balance by the use bodily fluid treatment devices, e.g., a dialysis apparatus. The present invention aims at providing a method for controlling a filtration rate during dialysis of the patient. Also, the present invention suggests devices applicable in the field or context of filtration rate control.
By utilization of the present invention a method for controlling a filtration rate during bodily fluid treatment by utilization of a device such as a device for blood treatment or dialysis is suggested. Also, a controller for carrying out the method according to the present invention is provided, as well as an apparatus, a device comprising a controller, a digital storage device, a computer program product, and a computer program.
In one aspect of the present invention, a method for controlling of a filtration rate during treatment, in particular blood treatment, and more particular dialysis, of a patient by utilization of a bodily fluid treatment device such as a dialysis device is proposed, comprising the step of defining a target relation, or a development thereof during blood treatment, between one or more calculated or measured value(s) reflecting the mass or the concentration or the volume of a substance comprised by a tissue or the bodily fluid of the patient and reflecting a distribution space of the patient or an approximation thereof, respectively, wherein during treatment or blood treatment, in particular, dialysis value(s) reflecting the mass or the concentration or the volume of the substance and/or reflecting the distribution space or an approximation thereof are repeatedly calculated or measured, and wherein the relation between the repeatedly calculated or measured values is determined at least once; and wherein the filtration rate of the bodily fluid treatment device is controlled such that the determined relation is identical or similar to the target relation or approaches it or aims to be or do so.
The patient can be either a human being or an animal. The patient may be sound or ill. The patient may be in need of medical care or not. The patient may be a dialysis patient or not.
In another aspect of the present invention, a controller is intended or provided or used or configured to carry out the method according to the present invention. The controller optionally comprises system(s) needed and suited and/or configured to carry out the respective steps of the method according to the present invention.
In particular, the controller comprises a target relation defining system configured for defining a target relation, or a development thereof during fluid treatment, between one or more calculated or measured value(s) reflecting the mass or the concentration or the volume of a substance comprised by a tissue or a bodily fluid of the patient, and one or more calculated or measured value(s) reflecting a distribution space of the patient or an approximation thereof; a calculation system configured for, during treatment of the bodily fluid, repeatedly calculating of value(s) reflecting the mass or the concentration or the volume of the substance and/or reflecting the distribution space or an approximation thereof, and determining the relation there between at least once; and a signal output system configured for outputting of one or more signals to a controlling system for controlling the filtration rate of the fluid treatment device such that the determined relation is or approaches the target relation or aims to do or be so.
In yet another aspect of the present invention, an apparatus is provided, the apparatus comprising system(s) for obtaining one or more value(s) reflecting or concerning the distribution space or an approximation or changes thereof of the patient's body, and/or system(s) for obtaining a value reflecting the mass, the volume or the concentration of the substance or changes thereof. The apparatus further comprises at least one controller according to the present invention.
In another aspect of the present invention, the apparatus comprises at least one controller according to the present invention or at least one apparatus according to the present invention.
In another aspect of the present invention, a digital storage device, in particular a disc, CD or DVD, has electrically readable control signals which are able to interact with a programmable computer system such that the method according to the present invention will be executed.
In another aspect of the present invention, a computer program product has a program code stored on a machine readable data medium for executing the method according to the present invention when executing the computer program product on a computer.
In another aspect of the present invention, a computer program has a program code for the execution of a method according to the present invention when executing the program on a computer.
Embodiments can include one or more of the following features.
In some embodiments, the target relation is predetermined or preset.
In certain embodiments, the target relation is defined by a target range or one or more target line(s).
In some embodiments, the target range is a combination of one or more thresholds.
In certain embodiments, the target line or range is a trajectory in a diagram, preferably in a diagram in which a no-refill-curve might also be or is illustrated. Also, preferably, the target line or range is a trajectory in a diagram depicting a value representing the mass, concentration or volume of a substance (or changes thereof) as referred to herein over a distribution space (or changes thereof)—or vice versa.
In some embodiments, the target relation is defined before starting the respective dialysis treatment. In certain embodiments, the target relation is defined during the respective dialysis treatment.
In some embodiments, the controlling of a filtration rate during dialysis is an intentional step. In these embodiments, the result of the control as regards the filtration rate is not to be mixed up with results achieved by chance or at random or in an uncontrolled manner.
In certain embodiments, the method according to the present invention comprises the step of determining or measuring the blood volume BVo in the normohydrated condition (i.e., with a relative overhydration of about 0 liter) of the patient.
In some embodiments, the blood volume BVo can be determined by a body composition measurement using the following equation:BV0=0.1×LTM+0.01×ATM  (1)with LTM being the lean tissue mass and ATM being the adipose tissue mass. Both LTM and ATM can be measured with monitors available in the market.
In certain embodiments, the blood volume BVo can be determined by the use of a anthropometric blood volume equation. In certain embodiments, the following formula by Nadler et al. is used:
For males:BVo=0.3669×(height of the person at issue in meter)3+0.03219×weight of that person in kg+0.6041  (1a)
For females:BVo=0.3561×height3 (in meter)+0.03308×weight in kg+0.1833  (1b)as published in Nadler, S. B., Hidalgo, J. U. and Block, T.: “Prediction of Blood Volume in Normal Human Adults.” Surgery, 51, 224-232, 1962.
In some embodiments, the method according to the present invention comprises the step of determining or measuring a maximum-refill curve or steady-state curve of the patient. In certain embodiments, the maximum-refill curve or steady-state curve is one boundary or limit of the target range for the relation.
The course of the maximum-refill curve or steady-state curve of the patient is in certain embodiments calculated or identified as follows:
The concentration c_Hb (also referred to in the following equations as “Hb”) of hemoglobin (Hb) depends on the mass m_Hb (or mHb) of Hb and the present blood volume BV of a given point of time as follows:
                              H          ⁢                                          ⁢          b                =                              m            Hb                    BV                                    (        2        )            
BV in turn is the sum of the blood volume BVo at normohydrated conditions and the overhydration volume stored within the blood vessel system. The latter can be calculated by utilization of the slope of the Guyton curve being a curve depicting the blood volume BV over the extracellular fluid volume ECW of a patient explaining physiologic interdependencies between extracellular water (ECW) and the blood volume. The overhydration volume stored within the blood vessel system equals K_Guyton*OH, with K_Guyton being the slope of the Guyton curve:
                              H          ⁢                                          ⁢          b                =                                            m              Hb                                                      BV                0                            +                                                k                  Guyton                                ×                OH                                              =                      1                                                            BV                  0                                                  m                  Hb                                            +                                                                    k                    Guyton                                                        m                    Hb                                                  ×                O                ⁢                                                                  ⁢                H                                                                        (        3        )            
That way, the relation between concentration c_Hb of Hb and the overhydration OH can be expressed by
                              H          ⁢                                          ⁢          b                =                                            1                              b                +                                  a                  ×                  OH                                                      ⁢            with            ⁢                                                  ⁢            b                    =                                                                      BV                  0                                                  m                  Hb                                            ⁢                                                          ⁢              and              ⁢                                                          ⁢              a                        =                                          k                Guyton                                            m                Hb                                                                        (        4        )            
Hence, by assessing the patient's hemoglobin concentration c_Hb over overhydration OH or over relative overhydration relOH before starting a dialysis treatment, one will get data that can be used for drafting or approximating the steady-state-curve or maximum-refill curve of that patient before starting a dialysis treatment or at the beginning thereof. As is obvious, the course of that curve can be drafted the more precisely the more constant m_Hb of Hb is for that patient. Also, the steady-state-curve or maximum-refill curve is more precise in the linear sections of the Guyton curve.
As can be seen from equation (4), from the approximated parameter b and by use of BVo, the total mass m_Hb of Hb can be determined; also, from parameter a and the total mass m_Hb of Hb the slope K_Guyton of the curve can be determined.
It is noted that the steady-state curve can be determined, approximated or drawn once two data gained or measured independently from each other or at different time points are known as well as BVo. In all other cases, as few as three data gained form different measurements will do as well.
In certain embodiments, the course of the steady-state curve is approximated based on only two measurement data as follows:
Before dialysis treatment, AEOH_pre and Hb_pre are measured (e.g. by the utilization of monitors commercially available from the present applicant). In certain embodiments, during dialysis treatment, a sufficiently strong UF bolus—that is, a suddenly increased ultrafiltration rate—is applied. In sufficient time before the dialysis treatment is terminated, the ultrafiltration is terminated for achieving a stable value called Hb_post indicating a Hb concentration. Once the refill process has been awaited and taken place, a value for AEOH_post is calculated by use of the ultrafiltration volume UFV. The steady-state curve (as is shown, e.g., in FIG. 1) can be approximated based on AEOH_pre, AEOH_post, Hb_pre, and Hb_post.
In some embodiments, a number of minor boluses is applied yielding the same result as is achieved with one strong bolus.
In certain embodiments, no bolus is applied at all. For example, if the filtration rate is set such that during filtration a maximum refill is achieved, the course of the treatment takes place just on the steady state curve.
In some embodiments, the course of the steady-state curve is approximated based on only two arbitrarily chosen measurement data. One exemplary procedure in which the curve is approximated on just two measurement data can be described as follows:
Before dialysis treatment, AEOH_pre is measured. During dialysis treatment, a rather low ultrafiltration rate is set such that a refill process can be observed or achieved from the onset or the very beginning of the dialysis. From the present ultrafiltration volume UFV and AEOH_pre, the present value for AEOH can be calculated. The present value for Hb can be determined by utilization of the blood volume monitor.
In some embodiments, the at least one value reflecting the mass, the volume or the concentration of the substance was obtained from blood samples.
In certain embodiments, the substance is comprised by the group comprising at least any protein produced naturally in the body of the patient, in particular hemoglobin (short: Hb), albumin, insulin, glucose, c-reactive protein (short: CRP), and non endogeneous substances, in particular pharmaceutically effective substances.
In some embodiments, the mass, the volume or the concentration of the substance or changes thereof is an indicator of the anemia state of the patient.
In certain embodiments, the anemia state of the patient is defined by the utilization of direct or indirect measurements or calculations of the mass, the concentration or the volume of a substance, e.g. hemoglobin (Hb), or changes over time thereof.
In some embodiments, the anemia state of the patient is defined by the utilization of direct or indirect measurements or calculations of the hematocrit (Hct) or changes over time thereof.
In some embodiments, the distribution space of the patient is an either measured or calculated value of the blood volume (BV). In certain embodiments, the distribution space is the blood volume at the beginning of another treatment session including filtration of the blood. In some embodiments, the distribution space is the intravascular blood volume. In certain embodiments, the distribution space and/or the blood volume encompasses the volume of the tube system of an extracorporeal blood system or parts thereof that is/are filled with blood. In certain embodiments, those parts may amount to 100, 150 or more milliliters (ml). For example, those parts comprise 130 ml with the applicant's dialysis device of the 5008 type (and 170 ml when used for Single Needle applications), and 170 ml with the applicant's dialysis device of the 2008 or 4008 type (and 210 ml when used for Single Needle applications). Also, in some embodiments, the blood capacity of the filter is also considered as part of the blood volume and/or the distribution space. The blood volume comprised by the filter may amount to 74 ml (FX60 by Fresenius, Germany) or about 100 ml (FX80 by Fresenius, Germany).
In some embodiments, the distribution space of the patient is an approximation based on either measured or calculated values reflecting the relative overhydration (relOH) of the patient.
In certain embodiments, the distribution space is defined as the ECW (extracellular water), the extracellular volume or fluid, the ICW (intracellular water), the intracellular volume or fluid, the plasma volume, the TBW (total body water), the liquor, the volume of oedema, lymph, urine, or any other bodily fluid or volume, and also combinations thereof. Also, the distribution space within the meaning of the present invention can be any ratio of volumes as mentioned before, e.g. ECW/ICW, etc.
In some embodiments, a target range for the target relation is defined in a diagram reflecting the mass or the concentration of the substance and the distribution space or the approximation thereof.
In certain embodiments, the method comprises the step of calculating a no-refill-curve.
In some embodiments, values that lie on the no-refill-curve are considered as a edge of a target range for the target relation.
In certain embodiments, the no-refill-curve relates to the state (which may change during dialysis and depending on the relative overhydration of the patient treated by dialysis) in which the blood volume is decreased by the same amount as is the (ultra)filtration volume (per time unit). As a result, the blood volume BV decreases quickly, and the Hb concentration c_Hb increases in turn. The no-refill-curve can delimit a no-refill-area (in a figure, for example) or no-refill-condition (in a patient, for example) from a refill-area or a refill-condition.
In some embodiments, the method according to the present invention comprises the step of calculating and/or measuring parameters reflecting the mass or the concentration of the substance and/or the distribution space of the patient or an approximation thereof.
In some embodiments, the method further includes assessing the size of at least one distribution space based on measured values and/or results of calculations reflecting a hemoglobin (Hb) state. The hemoglobin (Hb) state may be reflected by the Hb concentration, its total mass, its volume, change thereof over time, respectively, etc.
In certain embodiments, the method further includes assessing the size of at least one distribution space based on measured values and/or results of calculations reflecting the hematocrit (Hct) or changes thereof over time.
As is evident to the skilled person, the assessment of the size of at least one distribution space is not limited to be based on measured values and/or results of calculations reflecting a hemoglobin (Hb) state or the hematocrit (Hct) or changes thereof. The present invention can of course also be carried out based on measured values and/or results of calculations reflecting a mass, concentration or volume (and changes thereof) of any other suitable substance or marker.
In some embodiments, the method further includes using the size of at least one distribution space as obtained based on results from measurement of blood samples and/or from blood comprised in extracorporeal blood lines by utilization of an appropriate monitor. The measurements can be made by measuring the optical properties of the blood by optical sensors and/or by assessing acoustic properties like transit times and/or propagation velocities of ultrasonic pulses by ultrasonic sensors.
For determining the hydration state also any appropriate monitor can be used, such as monitors based on bioimpedance or dilution techniques.
In certain embodiments, the method further includes using the size of at least one distribution space as obtained based on results from urine samples.
In some embodiments, the method further includes using the size of at least one distribution space as obtained based on results from tissue samples.
In certain embodiments, the method further includes plotting results of the control for visual assessment.
In certain embodiments, the apparatus for controlling of a filtration rate during dialysis comprises a system for obtaining a value reflecting the distribution space or an approximation or changes thereof of the patient's body, and/or a system for obtaining a value reflecting the mass, the volume or the concentration of the substance or changes thereof. In these embodiments, the apparatus comprises at least one controller according to the present invention.
In some embodiments, the apparatus according to the present invention comprises a system for measuring or calculating the distribution space or an approximation or changes thereof, in particular for measuring or calculating the hydration state or an overhydration, or wherein the system for obtaining a value consists of such a system for measuring or calculating.
In certain embodiments, the apparatus comprises a system for obtaining a value reflecting the mass, the volume or the concentration of the substance that comprises at least one of a weight system, a system for determining the blood volume of the patient, a keyboard, a touch screen, a system for measuring or calculating the concentration, the volume and/or the mass of the substance, in particular hemoglobin (Hb) in blood, or changes thereof, or wherein the system for obtaining a value consists of such system for measuring or calculating.
In some embodiments, the apparatus according to the present invention comprises a system configured and intended for determining or assessing the relation between values.
In certain embodiments, the apparatus is or comprises a monitor for obtaining information concerning the control.
In some embodiments, the system for measuring or calculating the distribution space or an approximation or changes thereof is a monitor as described in WO 2006/002685 A1. The respective disclosure of WO 2006/002685 A1 is hereby incorporated in the present application by way of reference. Of course, the present invention must not be understood to be limited to systems or monitors obtaining data by bioimpedance measurements as is described in WO 2006/002685 A1. Other bioimpedance methods known in the art and also any other methods known in the art such as dilution measurements and also any other method known to the skilled person are also contemplated and encompassed by the present invention as well.
In certain embodiments, the apparatus comprises a system or monitor for measuring Hb concentrations (e.g., in [g/dl]) and/or for determining the blood volume by the utilization of any monitor as described in “Replacement of Renal Function by Dialysis” by Drukker, Parson and Maher, Kluwer Academic Publisher, 5th edition, 2004, Dordrecht, The Netherlands, on pages 397 to 401 (“Hemodialysis machines and monitors”), the respective disclosure of which is hereby incorporated by way of reference.
In some embodiments, the system or monitor is configured to measure the blood volume and/or the concentration of the substance—in particular Hb—by measuring an electrical conductivity.
In certain embodiments, the system or monitor is configured to measure the blood volume and/or the concentration of the substance—in particular Hb—by measuring an optical density.
In some embodiments, the system or monitor is configured to measure the blood volume and/or the concentration of the substance—in particular Hb—by measuring a viscosity.
In certain embodiments, the system or monitor is configured to measure the blood volume and/or the concentration of the substance—in particular Hb—by measuring a density.
In some embodiments, the system or monitor comprises one or more corresponding probes and/or one or more sensors for carrying out the measurements such as electrical conductivity sensors, optical sensors, viscosity sensors, density sensors, and the like.
In certain embodiments, the apparatus furthermore comprises an output device for outputting results provided by the controller.
In some embodiments, the output device is a monitor having a display, a plotter, a printer or any other system for providing an output.
In certain embodiments, the output device is connected to an actuator for controlling administration of a substance to the patient.
In other embodiments, the device may be used for treating a patient (or the patient's blood) by hemofiltration, ultrafiltration, hemodialysis, etc.
The embodiments may provide one or more of the following advantages.
In some embodiments, the present invention provides information on how the filtration rate should be controlled or fixed. The information can be advantageously used to prevent certain decreases of the patient's blood pressure caused by the dialysis. Also, the occurrence of nausea, convulsions, emesis, vertigo, impaired vision and other symptoms frequently caused by the filtration procedure can advantageously be reduced or avoided.
In certain embodiments, the present invention provides information on how high the filtration rate may be set to both prevent unwanted blood pressure drops and to accomplish the dialysis treatment as quick as possible (i.e., so as not to waste the patient's time or not to bind him to the treatment site longer than required). The latter may happen the closer the relation is to relations forming a maximum-refill curve or steady-state curve as described above.
Other aspects, features, and advantages will be apparent from the description, figures, and claims.